Andrew Kau, MD, PhD, studies the interaction between airway microbiota and host factors such as gender or obesity in order to better understand the risk for chronic asthma and other allergic diseases.
Asthma airway microbiota can play a critical role in the development of chronic asthma. Researchers in the Kau Lab are specifically investigating how the gastrointestinal and airway microbiomes increase susceptibility for the development of allergic airway diseases.
Current research in the lab is focused on better understanding how specific microbes alter allergic immune responses. The lab also is involved in a clinical study comparing the gastrointestinal and airway microbiomes of healthy and asthmatic men and women to see if there are gender differences in how microbial ecology may impact mucosal immune function.
The ongoing research has led the development of new computational, microbiologic and sequencing tools to delve into the complex interrelationships between host factors and microbial ecosystems.
The Kau lab is part of the Center for Women’s Infectious Disease Research in the Division of Allergy and Immunology and the Department of Medicine at Washington University School of Medicine.
Lab Team
Andrew L. Kau, MD, PhD
Principal Investigator
Research Technicians
Anne Rosen
Research Technician II
Michael Lint
Research Technician II
Jamison Rucker
Research Technician II
Current Graduate Students
Ariel Hernandez Leyva
MSTP Student
Naomi Wilson
PhD Student
Jesus Santiago Borges
PhD Student
Select Publications
- Cell Rep. 2020 Nov 3;33(5):108331. doi: 10.1016/j.celrep.2020.108331.
- PLoS Pathog. 2019 Apr 25;15(4):e1007645. doi: 10.1371/journal.ppat.1007645.
- Sci Transl Med. 2015 Feb 25;7(276):276ra24. doi: 10.1126/scitranslmed.aaa4877.
Coming soon.
Research in the laboratory of Brian J. Laidlaw, PhD, focuses on understanding how immunological memory develops in order to identify new approaches to protect against newly emerging viruses and allergic disease.
Specifically, researchers in the lab study the transcriptional pathways that regulate the development and function of memory B cells. While memory B cells are essential for the induction of protective immunity following vaccination, unrestrained development of memory B cells can result in the induction of pathological states, such as allergic disease. Laidlaw is a pioneer in the field, having been the first to characterize memory B cell precursor cells while a postdoctoral fellow at the University of California-San Francisco. He subsequently developed the first in vivo method to screen factors driving memory B cell development and identified several transcription factors that modulate the development of memory B cells following viral infection.
Current Research
The Laidlaw lab uses advanced cellular immunology and sequencing approaches to identify novel regulators of memory B cell development and function.
One area of focus is understanding how the memory B cell response to viral infection and allergic disease is shaped by the tissue microenvironment. For example, the lab investigates the process by which memory B cells develop in the lungs following influenza infection. Lung-resident memory B cells are important regulators of protective immunity against influenza virus but are not induced by current vaccination approaches. Identification of how lung-resident memory B cells develop would enable new vaccination approaches that could promote enhanced protective immunity.
The lab uses Crispr-Cas9 and other genetic approaches to identify transcription factors driving memory B cell development and function. Understanding of the mechanisms by which these factors function will reveal new targets for therapies designed to enhance the B cell response and protect against newly emerging viral strains. Identification of novel therapeutic targets will also facilitate new approaches to resolve allergic disease by restricting memory B cell development and limiting the induction of pathogenic IgE antibodies.
Research in the lab is currently funded by an NIH/NIAID K22 career research grant.
Laboratory Team
Brian J. Laidlaw, PhD
Principal Investigator
Brittany Henry
Research Tech II
Chris Hanson
Research Tech II
Serena Chan
Undergraduate researcher
Frank Lin
Undergraduate researcher
Haley Pak
Undergraduate researcher
Select Publications
- Laidlaw, B.J.*, and Cyster, J. (2020). Transcriptional regulation of memory B cell differentiation. Nat. Rev.Immunol. 1-12. *Corresponding Author
- Laidlaw, B.J., Duan. L., Xu, Y., Vazquez, S.E., and Cyster, J. (2020) The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development. Nat. Immunol. 21, 1082-1093. PMCID: PMC7442689
- Laidlaw, B.J., Schmidt, T.H., Green, J.A., Allen, C.D.C., Okada, T., and Cyster, J. (2017) The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells. J. Exp. Med. 214 (3), 639–649. PMCID: PMC5339677
- Laidlaw, B.J., Gray, E.E., Zhang, Y., Ramirez-Valle, F., and Cyster, J. (2019) Sphingosine-1 phosphate receptor 2 restrains egress of gd T cells from the skin. J. Exp. Med. 216 (7), 1487-1496. PMCID: PMC6605748
- Laidlaw, B.J., Lu. Y., Amezquita, R.A., Weinstein, J.S., Vander Heiden J.A., Gupta, N.T., Kaech, S.M., and Craft, J. (2017). Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Sci. Immunol. 2 (16), eaan4767. PMCID: PMC5846620
Zhen Ren, MD, PhD, studies hereditary angioedema (HAE) and angioedema of unknown cause (AUC). She searches for biomarkers to better diagnose and treat AUC while also investigating the genomic associations that lead to clinical variability in patients with HAE.
HAE is a rare genetic disorder that presents as recurrent, unpredictable episodes of tissue swelling. More than half of all patients diagnosed with HAE experience laryngeal attacks, which can be life-threatening due to asphyxiation. There is, however, substantial variability in symptoms experienced among HAE patients. Some have frequent attacks while others have few.
Ren’s research focuses on the genetic and molecular mechanisms underlying the clinical variability among HAE patients. The pathogenesis of HAE is linked to mutations in the C1 esterase inhibitor (C1INH). A decrease in C1INH leads to over-production of bradykinin (BK), which causes increased vascular permeability and swelling. However, the level of C1INH does not predict which patients are more likely to experience severe angioedema attacks. In addition, an increasing number of HAE cases have normal functional C1INH. There are no available molecular diagnostic markers that can be used to diagnose these individuals, resulting in cases falling into the category of Angioedema of Unknown Cause (AUC). Ren’s research will potentially identify new biomarkers that can be used to diagnose patients with AUC.
Clinically, the Division of Allergy and Immunology oversees one of the largest centers in the Midwest dedicated to treatment and research of hereditary angioedema. Within the center, multiple pharmaceutical trials have led to FDA-approval of several prophylactic medications to treat the disease. There are numerous clinical trials under way in our clinical research center, including prophylactic therapy for non-histaminergic angioedema with normal C1-INH level, oral long-term prophylactic treatment for HAE and oral treatment for acute attacks of HAE.
Principal Investigator
Zhen Ren, MD, PhD
Instructor in Medicine
Division of Allergy and Immunology
Washington University School of Medicine
Ofer Zimmerman, MD, is interested in genetic susceptibility to infectious diseases, host-pathogen interaction and primary immunodeficiency disorders. Through his research, Zimmerman hopes to identify why particular infections pose a greater risk for some patients but not others.
He is particularly interested in the host-pathogen interaction and evolution of alphaviruses, which are mosquito-transmitted viruses that are responsible for a number of human and animal diseases.
Zimmerman studies Mxra8, a receptor for Chikungunya and other alphaviruses, and the role of human MXRA8 genetic polymorphisms in susceptibility to Chikungunya infection. In addition, Zimmerman researches the connection between Mxra8 structure and function to further define the evolution of alphaviruses.
Zimmerman also studies immune responses to COVID-19 vaccines in patients with primarily immunodeficiency syndromes.
In collaboration with the Division of Infectious Diseases, in a bench to bedside approach, Zimmerman studies genetic susceptibility to mycobacterial and fungal infections.
Principal Investigator
Ofer Zimmerman, MD
Instructor
Division of Allergy and Immunology
Department of Medicine
Washington University School of Medicine
Select Publications
- Kim AS*, Zimmerman O*, Fox JM, Nelson CA, Basore K, Zhang R, Durnell L, Desai C, Bullock C, Deem SL, Oppenheimer J, Shapiro B, Wang T, Cherry S, Coyne CB, Handley SA, Landis MJ, Fremont DH and Diamond MS. An evolutionary insertion in the Mxra8 receptor binding site confers resistance to alphavirus infection and pathogenesis. Cell Host Microbe. 2020 Mar 11;27(3):428-440.e9. doi: 10.1016/j.chom.2020.01.008. Epub 2020 Feb 18. PMID: 32075743
- Zimmerman O, Olbrich P, Uzel G, Freeman AF, Zerbe CS, Rosen LB, Rosenzweig S, Kuehn H, Holmes K, Stephany D, Ding L, Sampaio EP, Hsu AP, Holland SM. STAT1 gain-of-function mutations: high total STAT1 with normal dephosphorylation. Frontiers in Immunology. 2019 Jul.
- Zimmerman O*, Rösler B*, Zerbe CS, Rosen LB, Hsu AP, Uzel G, Freeman AF, Sampaio EP, Rosenzweig SD, Kuhen H, Kim T, Brooks KM, Kumar P, Wang X, Netea MG, Van de Veerdonk FL, Holland SM. Risks of Ruxolitinib in STAT1 gain of function associated severe fungal disease. Open Forum Infect Dis. 2017 Sep 22;4(4): ofx202. doi: 10.1093/ofid/ofx202. eCollection 2017 Fall.